Solution-phase parallel synthesis is becoming an important method to prepare small organic molecules to identify and optimize lead compounds in modern drug development. Efficient purification methods are needed to rapidly isolate products in high purity. Solid-phase scavenging is currently used to remove excess reagents and/or byproducts; however, because these reactions are biphasic, they tend to be slow and highly reactive scavengers are needed to ensure high yields. The experiments in this SBIR proposal will demonstrate the advantages of the use of fluorous (perfluoroalkyl tagged) scavengers over solid-phase scavengers. These advantages include the use of near-stoichiometric amounts of scavenger and increased speed and selectivity of the solution-phase fluorous reactions. The specific aims are: 1) Small scale (1-5 g) synthesis of new fluorous scavengers from three most important classes of scavengers: an electrophilic scavenger, a nucleophilic scavenger, and an acid scavenger. 2) Validation of these new scavengers for use in solution-phase synthesis. Validation will include: 1) measurement of HPLC retention times of representative scavenged products as a predictor for a successful fluorous solid-phase extraction, 2) execution of control solid-phase extraction experiments to ensure that scavenged products are retained, 3) development of a complete scavenging protocol for a representative reaction, and 4) measurement of the reactivity of the fluorous scavenger relative to a comparable resin-bound scavenger in the representative reaction. 3) Demonstration of the use of the new scavengers in a small solution-phase parallel synthesis exercise. Nine to twelve new compounds will be made with purification by fluorous scavenging followed by fluorous solid-phase extraction. The efficiency of the scavenging will be checked by standard spectroscopic and analytical techniques.